Isononyl acetate

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.4 with logKow as the primary descriptor.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material : 3,5,5-trimethylhexyl acetate
- Molecular formula : C11H22O2
- Molecular weight : 186.293 g/mol
- Smiles notation : C(C)(=O)OCCCCCCC(C)C
- InChl : 1S/C11H22O2/c1-10(2)8-6-4-5-7-9-13-11(3)12/h10H,4-9H2,1-3H3
- Substance type: Organic
- Physical state: Liquid

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Desmodesmus subspicatus (previous name: Scenedesmus subspicatus)

Test type:

static

Water media type:

freshwater

Total exposure duration:

72 h

Test temperature:

23.1 – 23.4°C

pH:

7.2-8.6

Reference substance (positive control):

not specified

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

119.521 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

growth rate

The prediction was based on dataset comprised from the following descriptors: EC50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and ( not "z") )  )  and ("aa" and ( not "ab") )  )  and ("ac" and ( not "ad") )  )  and ("ae" and ( not "af") )  )  and "ag" )  and ("ah" and "ai" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Esters (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Shiff base formation after aldehyde release AND AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters AND SN1 AND SN1 >> Nucleophilic attack after carbenium ion formation AND SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters AND SN2 AND SN2 >> Acylation AND SN2 >> Acylation >> Specific Acetate Esters AND SN2 >> Nucleophilic substitution at sp3 Carbon atom AND SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters by DNA binding by OASIS v.1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Esters by Acute aquatic toxicity MOA by OASIS

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Esters by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Schiff base formers OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Epoxides OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Phosphonic esters by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.4

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) ester group OR Acylation >> Acylation involving an activated (glucuronidated) ester group >> Arenecarboxylic Acid Esters OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> Active cyclic agents  OR AN2 OR AN2 >> Michael addition to activated double bonds OR AN2 >> Michael addition to activated double bonds >> alpha,beta-Unsaturated Carbonyls and Related Compounds OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters >> alpha,beta-Unsaturated Carboxylic Acids and Esters OR AN2 >> Michael-type addition to quinoid structures  OR AN2 >> Michael-type addition to quinoid structures  >> Substituted Phenols OR Michael addition OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Conjugated systems with electron withdrawing groups  OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Schiff base formation OR Schiff base formation >> Direct acting Schiff base formers OR Schiff base formation >> Direct acting Schiff base formers >> 1,2-Dicarbonyls and 1,3-Dicarbonyls  OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> (Thio)Phosphates  OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  by Protein binding by OASIS v1.4

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as No Data by Ultimate biodeg

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as > 100 days by Ultimate biodeg

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as -CH-   [linear] AND -CH2-  [linear] AND Ester   [-C(=O)-O-C] AND Methyl  [-CH3] by Bioaccumulation - metabolism alerts

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as -C=CH  [alkenyl hydrogen] by Bioaccumulation - metabolism alerts

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as -CH-   [linear] AND -CH2-  [linear] AND Ester   [-C(=O)-O-C] AND Methyl  [-CH3] by Bioaccumulation - metabolism alerts

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aromatic-H by Bioaccumulation - metabolism alerts

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as -CH-   [linear] AND -CH2-  [linear] AND Ester   [-C(=O)-O-C] AND Methyl  [-CH3] by Bioaccumulation - metabolism alerts

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Fluorine  [-F] by Bioaccumulation - metabolism alerts

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Acetoxy AND Carboxylic acid ester AND Isopropyl by Organic Functional groups

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as tert-Butyl by Organic Functional groups

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Acetoxy AND Carboxylic acid ester AND Isopropyl by Organic Functional groups

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Sulfide by Organic Functional groups

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Acetoxy AND Carboxylic acid ester AND Isopropyl by Organic Functional groups

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Carboxylic acid by Organic Functional groups

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Acetoxy AND Carboxylic acid ester AND Isopropyl by Organic Functional groups

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Carbonate by Organic Functional groups

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Acetoxy AND Carboxylic acid ester AND Isopropyl by Organic Functional groups

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Aryl halide by Organic Functional groups

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Carboxylic acid ester AND Isopropyl by Organic Functional groups (nested)

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as Cycloalkane by Organic Functional groups (nested)

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as Carboxylic acid ester AND Isopropyl by Organic Functional groups (nested)

Domain logical expression index: "ad"

Referential boundary: The target chemical should be classified as Sulfonic acid by Organic Functional groups (nested)

Domain logical expression index: "ae"

Referential boundary: The target chemical should be classified as Carboxylic acid ester AND Isopropyl by Organic Functional groups (nested)

Domain logical expression index: "af"

Referential boundary: The target chemical should be classified as Surfactants - Anionic by Organic Functional groups (nested)

Domain logical expression index: "ag"

Similarity boundary:Target: CC(C)CCCCCCOC(C)=O
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "ah"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.33

Domain logical expression index: "ai"

Parametric boundary:The target chemical should have a value of log Kow which is <= 14.2

Validity criteria fulfilled:

not specified

Conclusions:

The median Effective concentration (EC50) value for 3,5,5-trimethylhexyl acetate on Desmodesmus subspicatus in a 72 hour study was estimated to be 120 mg/L on the basis of effects on growth rate.

Executive summary:

Using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance 3,5,5-trimethylhexyl acetate (CAS no. 40379 -24 -6). EC50 value was estimated to be 120 mg/l for Desmodesmus subspicatus for 72 h duration. Based on this value it can be concluded that the substance 3,5,5-trimethylhexyl acetate is considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

Description of key information

Using the OECD QSAR toolbox version 3.4 (2017) with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance 3,5,5-trimethylhexyl acetate (CAS no. 40379 -24 -6). EC50 value was estimated to be 120 mg/l for Desmodesmus subspicatus for 72 h duration. Based on this value it can be concluded that the substance 3,5,5-trimethylhexyl acetate is considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

Key value for chemical safety assessment

EC50 for freshwater algae:

120 mg/L

Additional information

Predicted data for the target chemical 3,5,5-trimethylhexyl acetate (CAS No. 40379-24-6) and various supporting weight of evidence studies for its read across substanceswere reviewed for toxicity to aquatic algae and cyanobacteria endpoint to summarize the following information:

 

Short term toxicity on aquatic algae and cyanobacteria of target chemical3,5,5-trimethylhexyl acetate (CAS No. 40379-24-6) is predicted using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances (2017).On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance is estimated to be 120 mg/l for Desmodesmus subspicatus for 72 duration. Based on this value it can be concluded that the substance3,5,5-trimethylhexyl acetateis considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

 

In a weight of evidencestudy from experimental study report (ABITEC, s.r.o., Sustainability Support Services (Europe) AB, Study no. 112-14-2/SSS/2018, 2017) of the read across chemical Octyl Acetate (CAS no. 112-14-1), Freshwater algal growth inhibition test was carried out on Desmodesmus subspicatus with the substance read across Octyl Acetate according to OECD Guideline 201. The test substance was dissolved in OECD growth medium and tested at the limit concentration of 100 mg/l. Effects on the growth rate of the organism were studied. The effective concentration (EC2.1) for the test substance, Octyl Acetate, in Desmodesmus subspicatus was determined to be 100 mg/L. As the limit test was performed at 100 mg/l where only 2.1% inhibition of algal cells was occurred. Thus it was estimated that the EC50 concentration was greater than 100 mg/l. Based on this EC2.1 % inhibition value and after comparing with CLP criteria for aquatic classification of the substance it is concluded that the substance Octyl Acetate does not exhibit toxicity to aquatic algae (Desmodesmus subspicatus) and cannot be classified as toxic as per the CLP classification criteria.

 

For the read across chemical 2-methyl propyl acetate (CAS no. 110-19-0) from peer reviewed journal (G. BRINGMANN and R. KUHN; 1980), short term toxicity to Entosiphon Sulcatum study was carried out for 72 hrs.The study was based on the effects of the read across compound 2-methyl propyl acetate on Entosiphon Sulcatum in a static fresh water system. Test chemical of known concentration was prepared in sterile double distilled water.For maintenance of the test strain of Entosiphon sulcatum, continuously inoculate the expected requirednumber of stock cultures at 72 h or 96 h intervals. Forthis, mix 8 ml of stock solution I and 8 ml of steriledouble-distilled water in 300-ml Erlenmeyer flasksstoppered with metal caps and add 2 ml of a stock culture and 2 ml of the adjusted bacterial suspensionfor Entosiphon stock cultures. Store stock cultures at25°C. Before inoculation control the flasks containingthe stock cultures by means of an inverse microscope.Escherichia coliwas used as a feeding material of the test organism Entosiphon sulcatum. Prepare two parallel dilution series in 300-ml Erlenmeyer flasks stoppered with metal caps. The dilutions will contain 1 part v/v each of pollutant solution in 20to 214partsv/vof mixture. Test vessel contain the known conc. of chemical and test organism. Leave the test culture at 25ᵒC for 72 hrs. Before measurement, control each flask by means of an inverse microscope. Add 10% of a 1.1% NaNO3 solution in double-distilled water filtered through a membrane filter (pore size 0.2/µm), and determine the number of protozoaby means of a cell counter.Pollutant concentrations at which the onset of inhibitory action was observed have been obtained by mathematical evaluation of counts. The term counts corresponds to impulses indicated by the coulter counter.Based on the onset of the inhibitory effect on population of the test organismEntosiphon Sulcatum, the 72 hr LOEC value was determined to be 411 mg/l, respectively and therefore, the 72 hr EC50 value was expected to be > 411 mg/l. Thus, based on the EC50 value (> 411 mg/l), it can be concluded that the substance 2-methyl propyl acetate can be considered as non-toxic to aquatic organisms and thus can be considered to be not classified as per the CLP classification criteria.

 

Another short term toxicity to green algae study was carried out for 72 hrs for the read across compound 2-methyl propyl acetate (CAS no. 110-19-0) (J-CHECK, 2017). The study was based on the effects of the read across compound 2-methyl propyl acetate on green algae in a static fresh water system. Based on effect on growth rate of the test organism green algae, the 72 hr EC50 and NOEC value was determined to be 370 and 95 mg/l, respectively and on the basis of AUG, the 72 hr EC50 and NOEC value was determined to be 250 and 110 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the substance 2-methyl propyl acetate can be considered as non-toxic to aquatic organisms and thus can be considered to be not classified as per the CLP classification criteria.

 

For the same read across chemical 2-methyl propyl acetate (CAS no. 110-19-0) from authoritative database (HSDB and Ecotox, 2017), short term toxicity to Chlorococcales (green algae) study was carried out for 24 hrs. The study was based on the effects of the test compound 2-methyl propyl acetate(CAS no. 110-19-0) on Chlorococcales in a static fresh water system. Chlorococcales (green algae) was used as a test organism. Based on effect on physiology of the test organism Chlorococcales, the 24 hr EC50 value was determined to be 600 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the substance 2-methyl propyl acetate can be considered as non-toxic to aquatic organisms and thus can be considered to be not classified as per the CLP classification criteria.

 

In a weight of evidence study from peer reviewed journal (Monika Nendzal and Andrea Wenzel, 2006) of the read across chemical 2-methylpropyl 2-methylprop-2-enoate (CAS no. 97-86-9), short term toxicity to Scenedesmus subspicatus (green algae) study was carried out for 30 or 60 mins. The study was based on the effects of the read across compound 2-methylpropyl 2-methylprop-2-enoate(CAS no. 97-86-9) on Scenedesmus subspicatus in a static fresh water system. Inhibition of photosynthesis (EC50) was determined from effects on O2-production in unicellular green algae Scenedesmussubspicatus, cultured according to OECD-Guideline No. 201. 5 ml of algae suspension (2 million cells/ml) were collected on a filter paper disk (diameter 13 mm). After incubation in test solution for 30 or 60 min, the disk was placed on top of the electrode of the measuring chamber (PHOSY-Mess 2000, Specht, Germany). The Clark-electrode was placed in the measuring chamber (25°C, 100% exposure (ca. 1.9 klux), measuring solution: 0.05 M KHCO3). After a dark phase of 5 min (O2 fell to nearly 0 mg/l), the O2-production [mg/l] was recorded for 14 min. On the basis of inhibition of photosynthesis of the test organism Scenedesmus subspicatus (green algae), the EC50 value was determined to be 442 mg/l, respectively. Thus, based on this value, it can be concluded that the substance 2-methylpropyl 2-methylprop-2-enoate can be considered as non-toxic to aquatic organisms and thus cannot be classified as hazardous as per the CLP criteria.

 

Thus, based on the overall reported results for target chemical3,5,5-trimethylhexyl acetate(OECD QSAR toolbox version 3.4, 2017) and for its read across substance (from study report,authoritative database J-CHECK, HSDB, ECOTOX and peer reviewed journals),it can be concluded that the test substance3,5,5-trimethylhexyl acetatecan be considered as non-toxic to aquatic environment and can be considered to be notclassified as per the CLP classification criteria.